Conjugation of p-nitroanisole and p-nitrophenol in hepatocytes isolated from streptozotocin diabetic rats.
The conjugative metabolism of p-nitroanisole (pNA) and p-nitrophenol (pNP) was studied in isolated hepatocytes of male and female rats rendered diabetic with streptozotocin. Hepatocytes of male diabetic rats formed more of the glucuronide conjugate from pNA than controls and a tendency toward higher sulfate conjugate production was observed. By summation of conjugated metabolites and unconjugated phenol, it was determined that O-demethylation of pNA was also increased, possibly accounting for the increased production of conjugated metabolites. Production of the sulfate conjugate directly from pNP was inhibited in male diabetic hepatocytes when the substrate concentration was 50 microM but was not altered at other substrate concentrations. Glucuronidation was increased in hepatocytes of diabetic rats when pNP was used as substrate at concentrations of 50 and 100 microM, whereas there was no difference from control at 25 microM pNP. Treatment of diabetic rats with insulin returned glucuronidation to control values. The effect of diabetes on glucuronidation in hepatocytes was not due to increases in microsomal glucuronyltransferase activity. In contrast to males, no differences were observed between hepatocytes of control and diabetic female rats in the capacity to form conjugated metabolites from pNA or pNP. It is consistent with previous reports that alterations in carbohydrate metabolism in hepatocytes of male diabetic rats led to accelerated formation of uridine diphosphate glucuronic acid, resulting in greater rates of glucuronidation.
D000818:Animals; D000840:Anisoles / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009596:Nitrophenols / Q000378:metabolism*; D051381:Rats; D012737:Sex Factors; D013431:Sulfates / Q000378:metabolism
D000840:Anisoles; D005965:Glucuronates; D009596:Nitrophenols; D013431:Sulfates; D014453:Glucuronosyltransferase; C005306:4-nitroanisole; C024836:4-nitrophenol